Self-organizing, or self-assembling, structures are known. A common example is liposomes. Liposomes are made by emulsifying amphiphilic (and optionally hydrophobic or lipophilic) molecules in water, preferably in the presence of surfactant. Liposomes are either unilamellar or multilamellar spheres that are manufactured from a variety of lipids. Drugs, for example, can be encapsulated within liposomes or captured within the liposome membrane.
Self-assembled structures known in the prior art have often exhibited limited stability that induces, for example, a rapid clearance of drug-loaded vesicles from the blood after their intravascular administration. Various approaches to increasing stability have included cross-linked liposomes, which are more resistant to degradation. Liposomes having “pegylated” surfaces, i.e. surfaces having coated thereon or bonded thereto polyethylene glycol, have longer circulating times following administration to a patient. Other methods to prepare liposomes with enhanced stability include preparation techniques such as emulsion polymerization and interfacial polymerization. However, these techniques require rather aggressive reaction conditions, so sensitive substances cannot be used during these procedures. The stability of liposomes can be enhanced by surface grafting of hydrophilic polymers or by polymerization of reactive lipid molecules in the vesicular aggregates. Recently, a similar mechanical stabilization of vesicles was obtained by swelling the lipid bilayer of vesicles with hydrophobic monomers, which were subsequently polymerized.
Other approaches for the preparation of nanometer to micrometer-sized spherical polymer shells involve the layer-by-layer deposition of polyelectrolytes on the surface of a charged nanoparticle followed by the dissolution of the templating particle or the shelf-assembly of amphiphilic diblock copolymers into micelles, selective cross-linking of their hydrophilic shell, and subsequent degradation of the hydrophobic core. Although it has been known for several years that under suitable conditions amphiphilic block copolymers can aggregate spontaneously into vesicular structures, this direct formation of aggregates with a hollow sphere morphology has only been used in one case to prepare polymer nanocapsules. This approach used, however, a rather complex process. The formation of vesicles from a poly(isoprene)-block-poly(2-cinnamoylethyl methacrylate) (PI-PCEMA) diblock copolymer in hexane was followed by the photo-crosslinking of the PCEMA blocks and w subsequent selective hydroxylation of the PI blocks to make the hollow nanospheres soluble in water.
It is therefore an object of the present invention to provide new types of mechanically and chemically stable vesicles and nanocapsules, using the concept of self-organization of amphiphilic molecules.
It is a further object of the present invention to provide amphiphilic copolymers, in one example cross-linkable triblock copolymers, for use in the manufacture of these structures.
It is a further object to provide methods of making vesicles and nanocapsules from amphiphilic copolymers.
It is a further object to provide vesicles and nanocapsules made from amphiphilic copolymers having molecules inserted in the membrane wall, and methods of making such.